+ Giorgia Mangili MD Cristina Sigismondi MD IRCCS Ospedale San Raffaele, Milan Gynecology Oncology Department Prof. M.Candiani The presenter has no conflict of interest to declare. Fertility-sparing surgery in borderline and non epithelial ovarian tumors: State of the Art ESGO 2013 Liverpool

+

+ Borderline Ovarian Tumors (BOT)

+ Borderline Ovarian Tumors: Early Stage  Fertility-sparing treatment: INDIPENDENT PROGNOSTIC FACTOR FOR RECURRENCE  Rate of recurrence NO IMPACT ON SURVIVAL  Risk of lethal recurrence < 0.05% Unilateral Salpingo-oophorectomy + peritoneal staging 0-5% Radical Surgery 0-25% Unilateral salpingo-oophorectomy 10-42% Cystectomy Daraï et al. Hum Reprod Update Du Bois et al. Eur J Cancer. 2013

+ Serous Borderline Ovarian Tumors N° Median Age I stII stIII stRelapses Progression Deaths Cystectomy (33%) 20 USO (7%) 02 DOC Radical surgery (1.8%)1 7 DOC 1 DOD Total (9%) 310

+ Bilaterality in Borderline Ovarian tumors BILATERAL CYSTECTOMY (experimental group, n = 15) versus SALPINGO-OOPHORECTOMY AND CYSTECTOMY (control group, n = 17)  No difference in cumulative recurrence rate  Shorter time to first recurrence and higher rate of radical treatment  Better reproductive outcomes Human Reproduction. 2010

+  26 patients  All patients had a borderline histology at first recurrence  11 patients relapsed at least twice  2 patients had an invasive histology at 2-3 recurrence (1 DOD) “Fertility-preserving surgery remains a valuable alternative in young patients with recurrent BOT, in the form of a non-invasive ovarian lesion, who wish to start a pregnancy.” Human Reproduction. September 25, 2013

+ Advanced Stages BOT Fertility-sparing Treatment Series N. of conservative treatments N. Non invasive implants N. Invasive implants N. Ns implants RelapsesDeaths Zanetta, Prat, (invasive imp.) Longacre, NR 50 De Iaco, NR 40 Uzan, (non invasive imp.) Viganò, Song, Total (38%)2 (1.4%)

+ Stromal Ovarian Tumors

+ Granulosa cell tumors

+ Fertility-sparing Surgery in Granulosa Cell Tumors  Unilateral salpingo-oophorectomy  Peritoneal staging  Endometrial biopsy  NO contralateral biopsy  NO lymphadenectomy Conservative surgery can be offered to young women who desire to retain fertility Colombo et al. J Clin Oncol Thrall et al. Gynecol Oncol. 2012

+ Sertoli-Leydig Cell Tumors No difference in survival rate between conservative and radical surgery AuthorsN.Stage IConservative surgery Young and Scully (97.6%)143 (69%) Gui (100%)28 (70%) Sigismondi (86%)11 (52%) Bath (86.7%)13 (86%) Weng (78%)11 (47%)

+ Malignant germ cell ovarian tumors (MOGCT)

+ Fertility-sparing Surgery in MOGCT StudyConservativeDemolitive Total Patient n°Patient n°Survival n°(%)Patient n°Survival n°(%) Creasman et al (59.3%)19/19 (100%)13 (40.6%)11/13 (85%) Gershenson et al (71.4%)12/15 (80%)6 (28.5%)3/6 (50%) Schwartz (89.4%)17/17 (100%)2 (10.5%)2/2 (100%) Zanetta et al (81.6%)135/138 (98%)31 (18.3%)27/31 (87%) Khi et al (93.4%)43/43 (100%)6 (13%)6/6 (100%) Chan et al (58.5%)306/313 (98%)222 (41.5%)212/222 (96%) Tangjitgamol et al (71. 7%)83/89 (93%)35 (28.2%)32/35(91%) Mangili et al (74.8%)84/92 (91%)31 (25.2%)25/31 (81%) Total (68%)699 (96%)346 (32%)318 (91%) Except for Stage IA dysgerminoma and stage I immature teratoma CONSERVATIVE SURGERY + PEB

+ Bilateral MOGCT Bilaterality 4.3% (dysgerminoma 15%) USO+CYS+staging Residual disease could be intentionally left in order to spare fertility 3 patients reported (2 OSR, 1 Vicus et al Gyn Onc 2010) If CYS is not possible? XY disgenetic gonads  bilateral gonadectomy, spare the uterus! 2 patients conceived through IVF with donor oocyte Mangili et al. Gyn ecol Oncol. 2011

+ Fertility Outcome in MOGCT Studyn°n° getting pregnancy Pektasides et al.175/17 (29.4%) Brewer et al143/14 (21.4%) Mitchell et al.2611/26 (42%) Low et al.7416/74 (21.6%) Zanetta et al.13832/138 (23.1%) Tangir et al.6429/64 (45.3%) Boran et al.236/23 (26%) de La Motte Rouge et al.4112/41 (29.2%) Cicin et al.297/29 (24.1%) Zanagnolo et al.7515/75 (20%) Weinberg et al.2210/22 (45.4%) Mangili et al.9212/92 (13%) Total615158/615 (25.7%) Premature ovarian failure 3%  Small number of patients  Short follow-up  Young patients

+ Reproductive function assessment after surgery plus chemotherapy for Germ Cell Ovarian Tumors: novel clues deriving from the field of fertility preservation Age Tumor characteristics StageTreatment AMH (ng/ml) 16 Mixed germ cell tumor IIIIC USO+ ovarian biopsy+ staging+ BEP Mixed germ cell tumor IIB USO+ CYS+ staging+ BEP0.7 21DysgerminomaICUSO+BEP2.3 23DysgerminomaIV USO+BEP 2.7 Oocytes cryopreservation Ottolina et al. Submitted

+ The Fertility Window Evaluation of ovarian reserve AMH Preservation of fertility Ovarian reserve NO DESIRE FOR PREGNANCY Spontaneous conception/ ART YES La Marca et al. Eur J Obstet Gynecol Reprod Biol. 2012

+ Conclusions Fertility-sparing surgery in borderline ovarian tumors and non epithelial ovarian cancers is feasible The fertility window may be shortened by oncological treatments Reproductive function&Oncological follow-up is required

+ Thank you!